DAVID NACHMANSOHN AND IRWIN B. WILSON 



The ammonium ion of dimethylaminoethyl acetate, al- 

 though somewhat unusual for a tertiary ion in that it causes 

 depolarization, does so with very much less vigor than acetyl- 

 choline. How does the "extra" methyl group of acetylcholine 

 lead to such a marked promotion? A clue to this action is to be 

 found in the tetrahedral configuration of these ions. If the 

 fourth group is not to merely project into the surrounding 

 medium, in which case we should be at a loss to explain its 

 activity, there must occur a folding of the protein structure where- 

 by this fourth group is brought into the close contact with the 

 protein necessary for the operation of short-range molecular 

 forces. Such a change in receptor configuration could well be 

 associated with the changes in ionic permeability observed during 

 the propagated action potential. Let us assume, for preciseness, 

 that positively charged amino groups of a protein chain form an 

 obstacle in the pathway of sodium ion permeation through the 

 membrane. By a slight change in configuration of this protein 

 chain, so that a negative carboxyl group takes the place of the 

 amino group, the obstacle may be removed. Of course, a 

 number of other possibilities may be readily conceived. But 

 the fact that quaternary ions are so much more eflficient in de- 

 creasing the potential difference between inside and outside 

 than tertiary ions, in other words, activate the receptor much 

 more efficiently, indicates the remarkable parallelism with the 

 promoting function of the extra methyl group observed in the 

 case of the esterase and the acetylase. 



Gap between Biochemical Data and the Actions 

 of the Living Cell 



The essentiality of the acetylcholine system in the elemen- 

 tary process of conduction appears established beyond any 

 reasonable doubt. Studies of the precise mechanism by which 

 this system generates the electric potentials are in their initial 

 phase. The views presented are an attempt to integrate the 

 vast amount of biochemical and physicochemical data with the 



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